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The effects of mGlu7 receptor modulation in behavioural models sensitive to antidepressant action in two mouse strains.
MedLine Citation:
PMID:  23455446     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
There is increasing evidence suggesting a role of the neurotransmitter glutamate in depression. The metabotropic glutamate (mGlu) receptors are G-protein coupled receptors, which mediate a slow modulatory response to glutamate signalling. mGlu7 receptor is a presynaptic inhibitory autoreceptor showing great promise as a potential therapeutic target for the treatment of depression. Selective pharmacological modulators of mGlu7 receptor have been developed; the positive allosteric modulator AMN082 and the negative modulator 6-(4-methoxyphenyl)-5-methyl-3-(4-pyridinyl)-isoxazolo[4,5-c]pyridin-4(5H)-one hydrochloride (MMPIP). They remain to be extensively characterized in behavioural models sensitive to antidepressant action. Therefore, we assessed the effects of these compounds on behaviour in two different mouse strains using several preclinical tests sensitive to antidepressant pharmacological action. AMN082 (6 mg/kg) reduced immobility in the forced swim test and tail suspension test (TST) in both C57BL/6j and CD1 mice. In CD1 mice, MMPIP (10 and 30 mg/kg) significantly increased the time spent immobile in the TST, whereas this effect was restricted to a dose of 30 mg/kg in C57BL/6j mice. Administration of MMPIP with AMN082 partially attenuated the antidepressant-like effect of AMN082 in C57BL/6j mice in the forced swim test and the TST. However, this effect was absent from the CD1 strain. This further adds to the growing corpus of data promoting the targeting of mGlu7 receptor with the aim of achieving an antidepressant effect.
Authors:
Richard M O'Connor; John F Cryan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Behavioural pharmacology     Volume:  24     ISSN:  1473-5849     ISO Abbreviation:  Behav Pharmacol     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9013016     Medline TA:  Behav Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  105-13     Citation Subset:  IM    
Affiliation:
aDepartment of Anatomy and Neuroscience bAlimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
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